Negative attributes of mixed-valence memories strengthen over long retention intervals and the degree of enhancement is predicted by individual differences in state anxiety.

Abstract

Memories are multifaceted and can simultaneously contain positive and negative attributes. Here, we report that negative attributes of a mixed-valence memory dominate long-term recall. To induce a mixed-valence memory, running responses were randomly reinforced with either food (∼83% of trials) or footshock (∼17% of trials), or a noise conditioned stimulus (CS) was followed randomly with either food (∼80% of trials) or footshock (∼20% of trials). Control animals were consistently reinforced with only food. Mixed-valence training promoted unstable behavior (e.g., erratic approach and withdrawal from the food cup) and moderate levels of fear during the training regimens. After a 20-day retention interval, animals that were consistently reinforced with food exhibited intact approach responding, and similar responding was observed if animals were food deprived or satiated (i.e., the response was insensitive to motivation). However, animals that experienced the mixed-valence training expressed significantly enhanced and stable fear (consistent immobility) relative to the end of training, regardless of whether animals were food deprived or not, suggesting that fear transitioned to a state that was insensitive to motivation. The degree of fear expressed during long-term retention was predicted by measures of state anxiety obtained prior to the training, indicating that the enhancement of fear across the retention interval was related to individual differences in basal "anxiety." These results suggest that negative attributes of memories dominate long-term recall, particularly in animals expressing an anxious phenotype, and these observations have direct implications for the chronic nature of anxiety disorders and the exacerbation of fear that accompanies posttraumatic stress disorder.

Unpredictable Mixed-Valence Outcomes Induce a Chronic and Reversible Generalized Anxiety-like Phenotype in Male Mice

“…We have reported ( 34 ) that long-term memory of conflict favors the expression of fear memories, i.e., when tested 20 days after the conclusion of mixed-valence reinforcement, mice demonstrated an increase in the expression of fear when approaching the goal area (with its mixed-valence history of reinforcement). This increase in fear could reflect the impact of negativity biases on the expression of long-term memories ( 35 , 36 , 37 ).…”